{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T20:49:48Z","timestamp":1769633388487,"version":"3.49.0"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2014,9,18]],"date-time":"2014-09-18T00:00:00Z","timestamp":1410998400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1003837","type":"journal-article","created":{"date-parts":[[2014,9,18]],"date-time":"2014-09-18T17:58:30Z","timestamp":1411063110000},"page":"e1003837","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":62,"title":["A Systems Approach to Predict Oncometabolites via Context-Specific Genome-Scale Metabolic Networks"],"prefix":"10.1371","volume":"10","author":[{"given":"Hojung","family":"Nam","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Campodonico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aarash","family":"Bordbar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel R.","family":"Hyduke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangwoo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel C.","family":"Zielinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard O.","family":"Palsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2014,9,18]]},"reference":[{"key":"ref1","first-page":"319","article-title":"Ueber den stoffwechsel der tumoren","volume":"152","author":"O Warburg","year":"1924","journal-title":"Biochem Z"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"D Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"MG Vander Heiden","year":"2009","journal-title":"Science"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nrc2981","article-title":"Regulation of cancer cell metabolism","volume":"11","author":"RA Cairns","year":"2011","journal-title":"Nat Rev Cancer"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.ccr.2012.02.014","article-title":"Metabolic reprogramming: a cancer hallmark even warburg did not anticipate","volume":"21","author":"PS Ward","year":"2012","journal-title":"Cancer Cell"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/nature10860","article-title":"IDH mutation impairs histone demethylation and results in a block to cell differentiation","volume":"483","author":"C Lu","year":"2012","journal-title":"Nature"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ccr.2010.12.014","article-title":"Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases","volume":"19","author":"W Xu","year":"2011","journal-title":"Cancer Cell"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.ccr.2013.04.018","article-title":"SDH mutations establish a hypermethylator phenotype in paraganglioma","volume":"23","author":"E Letouze","year":"2013","journal-title":"Cancer Cell"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fonc.2012.00085","article-title":"The emerging role of fumarate as an oncometabolite","volume":"2","author":"M Yang","year":"2012","journal-title":"Front Oncol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1101\/gad.191056.112","article-title":"Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors","volume":"26","author":"M Xiao","year":"2012","journal-title":"Genes Dev"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1093\/hmg\/ddi227","article-title":"Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations","volume":"14","author":"PJ Pollard","year":"2005","journal-title":"Hum Mol Genet"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ccr.2005.06.017","article-title":"HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability","volume":"8","author":"JS Isaacs","year":"2005","journal-title":"Cancer Cell"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nm0311-291","article-title":"Metabolism unhinged: IDH mutations in cancer","volume":"17","author":"JR Prensner","year":"2011","journal-title":"Nat Med"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/nbt.2488","article-title":"A community-driven global reconstruction of human metabolism","volume":"31","author":"I Thiele","year":"2013","journal-title":"Nat Biotechnol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/msb.2011.65","article-title":"A comprehensive genome-scale reconstruction of Escherichia coli metabolism-2011","volume":"7","author":"JD Orth","year":"2011","journal-title":"Mol Syst Biol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1365-2796.2011.02494.x","article-title":"Using the reconstructed genome-scale human metabolic network to study physiology and pathology","volume":"271","author":"A Bordbar","year":"2012","journal-title":"J Intern Med"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.biotechadv.2011.07.021","article-title":"Fifteen years of large scale metabolic modeling of yeast: developments and impacts","volume":"30","author":"T Osterlund","year":"2012","journal-title":"Biotechnol Adv"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/msb.2013.18","article-title":"Basic and applied uses of genome-scale metabolic network reconstructions of Escherichia coli","volume":"9","author":"D McCloskey","year":"2013","journal-title":"Mol Syst Biol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"5572","DOI":"10.1158\/1078-0432.CCR-12-1856","article-title":"Predicting drug targets and biomarkers of cancer via genome-scale metabolic modeling","volume":"18","author":"L Jerby","year":"2012","journal-title":"Clin Cancer Res"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1073\/pnas.0610772104","article-title":"Global reconstruction of the human metabolic network based on genomic and bibliomic data","volume":"104","author":"NC Duarte","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"e1002018","DOI":"10.1371\/journal.pcbi.1002018","article-title":"Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect","volume":"7","author":"T Shlomi","year":"2011","journal-title":"PLoS Comput Biol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/msb.2011.35","article-title":"Predicting selective drug targets in cancer through metabolic networks","volume":"7","author":"O Folger","year":"2011","journal-title":"Mol Syst Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nature10363","article-title":"Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase","volume":"477","author":"C Frezza","year":"2011","journal-title":"Nature"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nature11003","article-title":"The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity","volume":"483","author":"J Barretina","year":"2012","journal-title":"Nature"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature11632","article-title":"An integrated map of genetic variation from 1,092 human genomes","volume":"491","year":"2012","journal-title":"Nature"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.1215040","article-title":"A systematic survey of loss-of-function variants in human protein-coding genes","volume":"335","author":"DG MacArthur","year":"2012","journal-title":"Science"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1093\/nar\/gkr407","article-title":"Predicting the functional impact of protein mutations: application to cancer genomics","volume":"39","author":"B Reva","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1186\/1471-2164-14-S3-S7","article-title":"Assessment of computational methods for predicting the effects of missense mutations in human cancers","volume":"14","author":"F Gnad","year":"2013","journal-title":"BMC Genomics"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/73432","article-title":"Systematic variation in gene expression patterns in human cancer cell lines","volume":"24","author":"DT Ross","year":"2000","journal-title":"Nat Genet"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1093\/bioinformatics\/btr413","article-title":"RxnFinder: biochemical reaction search engines using molecular structures, molecular fragments and reaction similarity","volume":"27","author":"QN Hu","year":"2011","journal-title":"Bioinformatics"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1093\/bioinformatics\/btp507","article-title":"Metabolite and reaction inference based on enzyme specificities","volume":"25","author":"MJ de Groot","year":"2009","journal-title":"Bioinformatics"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1021\/ci900104b","article-title":"Assignment of EC numbers to enzymatic reactions with MOLMAP reaction descriptors and random forests","volume":"49","author":"DA Latino","year":"2009","journal-title":"J Chem Inf Model"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"e52901","DOI":"10.1371\/journal.pone.0052901","article-title":"Assignment of EC Numbers to Enzymatic Reactions with Reaction Difference Fingerprints","volume":"7","author":"QN Hu","year":"2012","journal-title":"PLoS One"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"D783","DOI":"10.1093\/nar\/gkr799","article-title":"MACiE: exploring the diversity of biochemical reactions","volume":"40","author":"GL Holliday","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"D603","DOI":"10.1093\/nar\/gkn810","article-title":"HMDB: a knowledgebase for the human metabolome","volume":"37","author":"DS Wishart","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.cbpa.2009.11.028","article-title":"What makes an enzyme promiscuous?","volume":"14","author":"A Babtie","year":"2010","journal-title":"Curr Opin Chem Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1146\/annurev-biochem-030409-143718","article-title":"Enzyme promiscuity: a mechanistic and evolutionary perspective","volume":"79","author":"O Khersonsky","year":"2010","journal-title":"Annu Rev Biochem"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1126\/science.1234769","article-title":"Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation","volume":"340","author":"F Wang","year":"2013","journal-title":"Science"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1126\/science.1236062","article-title":"An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells","volume":"340","author":"D Rohle","year":"2013","journal-title":"Science"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1172\/JCI71180","article-title":"MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis","volume":"124","author":"A Terunuma","year":"2014","journal-title":"J Clin Invest"},{"key":"ref41","unstructured":"illumina (2011) RNA-seq Data Comparison with Gene Expression Microarrays. illumina White Paper: illumina."},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1038\/nprot.2011.308","article-title":"Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0","volume":"6","author":"J Schellenberger","year":"2011","journal-title":"Nat Protoc"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"e1000082","DOI":"10.1371\/journal.pcbi.1000082","article-title":"Context-specific metabolic networks are consistent with experiments","volume":"4","author":"SA Becker","year":"2008","journal-title":"PLoS Comput Biol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"5457","DOI":"10.1074\/jbc.R800048200","article-title":"Use of randomized sampling for analysis of metabolic networks","volume":"284","author":"J Schellenberger","year":"2009","journal-title":"J Biol Chem"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nbt.1614","article-title":"What is flux balance analysis?","volume":"28","author":"JD Orth","year":"2010","journal-title":"Nat Biotechnol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/msb.2010.47","article-title":"Omic data from evolved E. coli are consistent with computed optimal growth from genome-scale models","volume":"6","author":"NE Lewis","year":"2010","journal-title":"Mol Syst Biol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/msb.2010.68","article-title":"Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions","volume":"6","author":"A Bordbar","year":"2010","journal-title":"Mol Syst Biol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0006-3495(02)75150-3","article-title":"Energy balance for analysis of complex metabolic networks","volume":"83","author":"DA Beard","year":"2002","journal-title":"Biophys J"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1126\/science.1216861","article-title":"Network context and selection in the evolution to enzyme specificity","volume":"337","author":"H Nam","year":"2012","journal-title":"Science"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"20380","DOI":"10.1073\/pnas.0810485105","article-title":"Highly parallel identification of essential genes in cancer cells","volume":"105","author":"B Luo","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1093\/bioinformatics\/bti213","article-title":"Exploring the diversity of complex metabolic networks","volume":"21","author":"V Hatzimanikatis","year":"2005","journal-title":"Bioinformatics"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1002\/bit.22673","article-title":"Discovery and analysis of novel metabolic pathways for the biosynthesis of industrial chemicals: 3-hydroxypropanoate","volume":"106","author":"CS Henry","year":"2010","journal-title":"Biotechnol Bioeng"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nchembio.580","article-title":"Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol","volume":"7","author":"H Yim","year":"2011","journal-title":"Nat Chem Biol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1093\/bioinformatics\/btr177","article-title":"Prediction of metabolic reactions based on atomic and molecular properties of small-molecule compounds","volume":"27","author":"F Mu","year":"2011","journal-title":"Bioinformatics"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1002\/bit.22489","article-title":"Computational framework for predictive biodegradation","volume":"104","author":"SD Finley","year":"2009","journal-title":"Biotechnol Bioeng"},{"key":"ref56","unstructured":"James CA, Weininger D, Delany J (2004) Daylight theory manual. Aliso Viejo: Daylight chemical information systems, Inc."},{"key":"ref57","unstructured":"Silverman RB (2002) Organic Chemistry of Enzyme-Catalyzed Reactions: Academic Press."}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003837","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,2]],"date-time":"2024-06-02T17:41:58Z","timestamp":1717350118000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003837"}},"subtitle":[],"editor":[{"given":"Yanay","family":"Ofran","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2014,9,18]]},"references-count":57,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2014,9,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1003837","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,18]]}}}